Impact of multiple sclerosis on employment and income: Insights from a random sample representative of private sector employees in France using longitudinal administrative data.

In France, few data sources are available to estimate the impact of multiple sclerosis (MS) on job retention and its consequences on the level of resources, especially in large representative samples. The aim of the present study was to measure impact of MS on employment rates, wages and income (including unemployment benefit, sickness benefit and disability pension) by comparing work trajectories of people living with MS with those of a matched control group. We used the HYGIE database, which is the result of the linkage of two administrative databases in the private sector for a random sample of over 900,000 people. In order to identify the causal effect of MS on employment after 1 to 20 years, the difference-in-differences method with matching (age, sex, career and health history) was used, overall and in subgroups. The year of entry in long-term disease status for MS was used to approximate the onset of MS. Overall, 946 people with MS were included. Their situation was fairly favorable before MS (88.1% in employment, resources higher than the median for the general population), but MS had strong and continuous negative effects. Indeed, at 10 years, the employment rate fell by 28.6 percentage points (pp) and the disability pension allowance increased by 50.5 pp; the wage percentile fell by 19.2 pp and the replacement income accounted for a growing share of total income (+ 39.7 pp). Although administrative data had several strengths, clinical information on the severity of the disease or on its therapeutic management was not available. In conclusion, this study shows that the effects of MS on the employed population in the private sector occur early in the disease course and are cumulative, and that replacement income helps to reduce the loss of resources thanks to the French health and social system.

Prevalence of multiple sclerosis in France in 2021: Data from the French health insurance database.

BACKGROUND: France is among the countries with high prevalence of multiple sclerosis (MS). The most recent estimates are from 2012 and need to be updated because MS prevalence has increased worldwide. OBJECTIVE: To estimate MS prevalence in France on December 31, 2021 and to describe the characteristics of the French MS population using data from the French national health insurance database (SNDS). MATERIAL AND METHODS: Persons with MS (PwMS) were identified in the SNDS database (99% of national coverage) using an algorithm with three criteria: long-term disease status, hospitalizations, and MS-specific drug reimbursements. Crude and sex- and age-stratified prevalence rates were calculated with their 95% confidence intervals as well as the standardized prevalence stratified on the region of residence. RESULTS: In total, 134,062 PwMS were identified (71.8% of women, median age 53.0±14.8years) yielding a prevalence of 197.6 per 100,000 (95% CI [196.5-198.7]). Prevalence rates in women and men were respectively 274.9 (95% CI [273.2-276.6]) and 115.2 (95% CI [114.0-116.4]). In metropolitan France, the highest prevalence rates were observed in the northeastern regions (e.g.>230 PwMS per 100,000 in Grand Est and Hauts-de-France), and the lowest rates in the southwestern regions (∼180 PwMS per 100,000 in Nouvelle-Aquitaine and Occitanie). Overall, 32.1% of PwMS had another long-term disease and 51.8% received at least one MS-specific drug in 2021. CONCLUSION: MS prevalence in France has increased by ∼30% in the last 10years. This increase is probably linked to population ageing, longer survival of PwMS, and the long observation period. The part attributable to a possible increase in MS risk remains to be determined with incidence studies.

Ten-year follow-up after mitoxantrone induction for early highly active relapsing-remitting multiple sclerosis: An observational study of 100 consecutive patients.

BACKGROUND: Six monthly courses of mitoxantrone were approved in France in 2003 for patients with highly active multiple sclerosis (MS). OBJECTIVE: To report the 10-year clinical follow-up and safety of mitoxantrone as an induction drug followed by maintenance therapy in patients with early highly active relapsing-remitting MS (RRMS) and an Expanded Disability Status Scale (EDSS) score<4, 12months prior to mitoxantrone initiation. METHODS: In total, 100 consecutive patients with highly active RRMS from the Rennes EDMUS database received monthly mitoxantrone 20mg combined with methylprednisolone 1g for 3 (n=75) or 6months (n=25) followed by first-line disease-modifying drug (DMD). The 10-year clinical impact was studied through clinical activity, DMD exposure, and adverse events. RESULTS: Twenty-four percent were relapse-free over 10years and the mean annual number of relapses was 0.2 at 10years. The mean EDSS score remained significantly improved for up to 10years, changing from 3.5 at mitoxantrone initiation to 2.7 at 10years. The probability of disability worsening and improvement from mitoxantrone initiation to 10years were respectively 27% and 58%, and 13% converted to secondary progressive MS. Patients only remained untreated or treated with a first-line maintenance DMD for 6.5years in average. In our cohort, mitoxantrone was generally safe. No leukemia was observed and six patients developed neoplasms, including 4 solid cancers. CONCLUSION: Monthly mitoxantrone for 3 or 6months, followed by maintenance first-line treatment, may be an attractive therapeutic option for patients with early highly active RRMS, particularly in low-income countries.

Disease-modifying therapy usage in patients with multiple sclerosis in France: A 6-year population-based study.

BACKGROUND: Most data regarding the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) comes from clinical series or regional databases that have a risk of recruitment bias. French health administrative data offers the significant advantage of being extensive in regards to both MS population coverage and DMT prescriptions. OBJECTIVES: To describe patterns of DMTs usage at the level of the entire French population of MS patients from 2010 to 2015. METHODS: MS patients were identified during a 6-year study period via the French national health data system (covering 97% of the general population) and characteristics of patients who received at least one treatment were compared to those that never received treatment over the indicated period. A state sequence analysis was performed to study in a longitudinal way MS patients who started DMTs in 2010 and then to classify them into groups of similar therapeutic patterns. DMTs were categorized into first-line, second-line and off-label use, and included untreated periods for at least six months. Groups that were obtained were described and compared using a multinomial logistic regression. RESULTS: A total of 112,415 patients with MS were identified, of whom 54.0% received at least one DMT over the 6 years. The probability of being treated significantly decreased with age. Comorbidities and physical limitations appeared to be more frequent in not treated patients than in treated patients. Significant differences were also found between the two groups regarding the use of healthcare services (hospitalizations and visits to general practitioner, neurologist and nurse). Based on the 6-year therapeutic sequences, a four-cluster typology was obtained on the 4,474 patients who started a DMT in 2010. The first group which consisted of more than half of the patients (57.0%) mainly used first-line DMTs. The second group (13.1%) represented patients with second-line DMTs whereas the third group (7.3%) was comprised of off-label users and the last group (22.6%) was composed of MS patients who received no or minimal treatments. Classification into one of these groups was associated with patient's age, long-term disease status, pregnancy occurrence, estimated level of disability, levels of care (visits to a neurologist, nurse and/or physiotherapist and hospital/rehabilitation stays) and occurrence of death. CONCLUSIONS: The exhaustive population-based dataset from the French national health data system gave the opportunity to provide a detailed description regarding the use of DMTs for MS at national level. The innovative method of state sequence analysis allowed obtaining four homogeneous groups of patients among thousands of longitudinal therapeutic sequences. The predominant place of first-line treatments was confirmed even if the type of first-line treatments has probably changed since 2015.

Use of healthcare services by patients with multiple sclerosis in France over 2010-2015: a nationwide population-based study using health administrative data.

BACKGROUND: Most of the knowledge about people with multiple sclerosis (PwMS) in France comes from cohorts, which may suffer from recruitment bias or from the unique registry located in Lorraine, East France. OBJECTIVE: To describe use of care in the French population of PwMS, over 2010-2015. METHODS: All PwMS in the French national health data system (97% of the general population covered) were included. Demographics, and use of care were described (visits with general practitioners (GPs), neurologists, nurses, physiotherapists and hospitalisations). A focus on the neurological follow-up was also conducted. RESULTS: A total of 112,415 PwMS were identified (sex ratio F:M = 2.4, median age 46), of whom 5005 died during follow-up. The median numbers of visits with GPs and neurologists were 6.6 and 1.3 respectively per patient-year. Moreover, 53,457 (47.6%) received multiple sclerosis (MS) treatments; about 13% of patients had no neurological follow-up, and 81.8% had at least one hospitalisation. CONCLUSIONS: For the first time in France, this exhaustive dataset offered the opportunity to provide objective figures regarding care practices for MS at the national level, without any selection bias. It also allowed description of patients with MS according to their neurological follow-up, especially those who were absent from cohorts led by neurologists.

[Identification of neurodegenerative diseases in administrative databases in France: A systematic review of the literature]. / Identification des maladies neurodégénératives dans les bases de données médicoadministratives en France : revue systématique de la littérature.

BACKGROUND: Given the health, social and economic burden of neurodegenerative diseases (ND), the development of epidemiologic studies is required. Administrative databases, such as the French national health insurance database (SNIIRAM) could represent an opportunity for researchers. ND could be presumed from drug reimbursement data, hospital stays or registration of a chronic condition. The aim of this study was to describe, in French administrative databases, algorithms used to identify Alzheimer's disease and associated disorders (ADAD), Parkinson's disease and associated disorders (PDAD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). METHODS: A systematic literature review was performed in Medline and gray literature through December 31th, 2015. French studies focusing on ADAD, PDAD, MS or ALS as a primary health outcome, conducted among one of the SNIIRAM data sources (outpatient reimbursements, chronic condition registration, hospital discharge) were included. RESULTS: Thirty-four studies were included (ADAD, n=18, PDAD, n=9, MS, n=4, ALS, n=3), leading to 36 algorithms. For each studied ND, there was an important variability in the algorithms, concerning (i) the type of criteria used (administrative database versus multi-source systems); (ii) the number of criteria used; (iii) the definition used for each criteria. The extent and level of drug exposure highly varied. Identification through hospitalizations showed variations in terms of type of stay (short stay, long-term stay, psychiatric ward…), extent of diagnosis codes used, diagnosis type (principal, related, associated diagnosis) and period used. A validation study was conducted for 2 out of 36 algorithms (PDAD), and criteria completeness was estimated for 3 algorithms (MS, ALS). CONCLUSION: Despite the increase in ND identification among French administrative databases, few algorithms have been validated. Validation studies should be encouraged.

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond.

Air pollution (indoors and outdoors) is a major issue in public health as epidemiological studies have highlighted its numerous detrimental health consequences (notably, respiratory and cardiovascular pathological conditions). Over the past 15 years, air pollution has also been considered a potent environmental risk factor for neurological diseases and neuropathology. This review examines the impact of air pollution on children's brain development and the clinical, cognitive, brain structural and metabolic consequences. Long-term potential consequences for adults' brains and the effects on multiple sclerosis (MS) are also discussed. One challenge is to assess the effects of lifetime exposures to outdoor and indoor environmental pollutants, including occupational exposures: how much, for how long and what type. Diffuse neuroinflammation, damage to the neurovascular unit, and the production of autoantibodies to neural and tight-junction proteins are worrisome findings in children chronically exposed to concentrations above the current standards for ozone and fine particulate matter (PM2.5), and may constitute significant risk factors for the development of Alzheimer's disease later in life. Finally, data supporting the role of air pollution as a risk factor for MS are reviewed, focusing on the effects of PM10 and nitrogen oxides.

Epidemiology of multiple sclerosis.

Multiple sclerosis (MS) is the most frequently seen demyelinating disease, with a prevalence that varies considerably, from high levels in North America and Europe (>100/100,000 inhabitants) to low rates in Eastern Asia and sub-Saharan Africa (2/100,000 population). Knowledge of the geographical distribution of the disease and its survival data, and a better understanding of the natural history of the disease, have improved our understanding of the respective roles of endogenous and exogenous causes of MS. Concerning mortality, in a large French cohort of 27,603 patients, there was no difference between MS patients and controls in the first 20 years of the disease, although life expectancy was reduced by 6-7 years in MS patients. In 2004, the prevalence of MS in France was 94.7/100,000 population, according to data from the French National Health Insurance Agency for Salaried Workers (Caisse nationale d'assurance maladie des travailleurs Salariés [CNAM-TS]), which insures 87% of the French population. This prevalence was higher in the North and East of France. In several countries, including France, the gender ratio for MS incidence (women/men) went from 2/1 to 3/1 from the 1950s to the 2000s, but only for the relapsing-remitting form. As for risk factors of MS, the most pertinent environmental factors are infection with Epstein-Barr virus (EBV), especially if it arises after childhood and is symptomatic. The role of smoking in MS risk has been confirmed, but is modest. In contrast, vaccines, stress, traumatic events and allergies have not been identified as risk factors, while the involvement of vitamin D has yet to be confirmed. From a genetic point of view, the association between HLA-DRB1*15:01 and a high risk of MS has been known for decades. More recently, immunogenetic markers have been identified (IL2RA, IL7RA) and, in particular thanks to studies of genome-wide associations, more than 100 genetic variants have been reported. Most of these are involved in the immune response and often associated with other autoimmune diseases. Studies of the natural history of MS suggest it is a two-phase disease: in the first phase, inflammation is focal with flares; and in the second phase, disability progresses independently of focal inflammation. This has clear implications for therapy. Age may also be a key factor in the phenotype of the disease. In conclusion, France is a high-risk country for MS, but it only slightly reduces life expectancy. MS is a multifactorial disease and the implications of immunogenetics are major. Preventative approaches might be derived from knowledge of the risk factors and natural history of the disease (smoking, vitamin D).

Register-based incidence of multiple sclerosis in Brittany (north-western France), 2000-2001.

OBJECTIVES: To report on multiple sclerosis (MS) incidence in Brittany, north-western France. MATERIALS & METHODS: From 2000, we set up a population-based register for patients presenting a putative incident MS (PIMS), that is first symptoms compatible with MS onset. We used 3 medical sources of case ascertainment (neurologists, CSF, regional MS-Clinic). Eligibility criteria required both clinical onset and being permanent resident of Brittany in 2000 or 2001. From 2010, all medical records were tracked, the 10-year follow-up allowing previously reported data to be updated. RESULTS: Of 313 eligible PIMS, there were 208 definite MS (both McDonald and Poser criteria), 41 CIS-probable MS (Poser criteria), 32 CIS-possible MS and 32 non-MS. Our incident cohort of 249 MS cases with definite/probable MS (sex ratio 2.95) gave a crude annual incidence of 4.28 per 100,000 inhabitants (6.22 for women, 2.23 for men), and age-standardized rates (adjustment to the European population) of 4.41 [3.32-5.51], 6.68 [4.75-8.60], and 2.21 [1.12-3.31], respectively. Age-specific rates by gender and initial course showed that attack onset MS peaked at 25-29 years and progressive onset MS at 40-44 years in women (20-24 years and 45-49 years in men, respectively). CONCLUSIONS: Brittany is confirmed a high-risk region for MS. Our data show marked differences in sex-specific pattern of MS incidence by clinical course and point out 25- to 29-year-old women as having the highest MS risk. While temporal variations cannot be excluded, comparison with overall French data suggests that other factors rather than latitude may influence the MS risk in France.

Ten-year prognosis in multiple sclerosis: a better outcome in relapsing-remitting patients but not in primary progressive patients.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) prognosis remains a challenge for both patients and physicians. Complementary to natural history studies, updated population-based data from the first event suggestive of MS, at the time of the first approved disease modifying drug (DMD), are needed. Our objective was to provide a 10-year history of MS from clinical onset at time of first approved DMDs in a population-based cohort. METHODS: A population-based cohort of patients whose first clinical event suggestive of MS had occurred in Brittany between 2000 and 2001 was prospectively selected. History of relapses, treatments and disability up to 10 years after onset were collected. RESULTS: In all, 278 patients with either attack-onset (n = 244) or progressive-onset (n = 34) were recruited. Amongst attack-onset patients, 30% remained as clinically isolated syndrome and 70% had a second relapse after a median time of 1.7 years (95% confidence interval 1.2-2.4). 80% of relapsing-remitting MS patients received DMDs for at least 6 months. 29% reached disability status scale (DSS) 3 and 8% DSS 6. Amongst progressive-onset patients, 100% reached DSS 3 and 59% DSS 6. CONCLUSION(S): Our population-based study reports a lower risk of disability progression at 10-year follow-up in the relapsing-remitting MS group than previously reported. This better prognosis was not observed in the progressive-onset MS group. This finding impacts the prognosis given to patients in clinical practice.

Relevancy and reproducibility of magnetic resonance imaging (MRI) interpretation in multiple-ligament injuries and dislocations of the knee.

INTRODUCTION: After multiple-ligament injuries and dislocations of the knee, clinical assessment of the soft tissues is difficult and MRI is generally performed. HYPOTHESIS: MRI is a reliable examination, providing a precise and reproducible assessment of soft-tissue lesions after multiple-ligament injuries or dislocations of the knee. MATERIALS AND METHODS: Forty patients presenting multiple-ligament lesions of the knee were included in this multicenter prospective study. All had an MRI of the knee in the 48 h following their accident. Thirty-four patients were treated surgically. A 17-item standardized interpretation guide was created. Intraobserver reproducibility was assessed by comparing the interpretations of five surgeons at two different times 3 weeks apart. Interobserver reproducibility was evaluated by comparing the results of the interpretations of 40 MRIs performed by three pairs of surgeons. The relevance of the MRI interpretations was determined by comparing the results of the surgeons to those of a radiologist and with the data from the surgical reports. RESULTS: The overall intraobserver and interobserver agreement was low. Comparing the surgeon's results with the radiologist's results and the surgical data, the agreement was low. DISCUSSION: After multiple-ligament injuries and dislocations of the knee, a precise diagnosis is necessary. This study provides an isolated demonstration of the lack of precision and reproducibility of MRI interpretations for the diagnosis of the lesion's topography. MRI should be integrated into a complete assessment with a precise clinical exam and stress X-rays. LEVEL OF EVIDENCE: Level IV, prospective case-control study.

Knowledge of TIA among general practitioners and emergency department physicians. A questionnaire survey in a French semi-rural area.

BACKGROUND AND OBJECTIVE: Management of transient ischemic attacks (TIAs) is of vital importance in an attempt to prevent stroke. However, suboptimal management still raise concern among general practitioners (GPs) and emergency department (ED) physicians-the first medical contact of most TIA patients. This may relate to their poorly updated knowledge about TIA. The study was designed to assess knowledge of TIA among these non-neurologists. METHODS: The study was a post-mailed questionnaire survey among GPs and ED physicians. The questionnaire related to selective clinical aspects on TIA. RESULTS: There were a total of 85 respondents for analysis, mostly GPs (n=64; 75.3%), out of 177 mailed physicians. Response rate was 52.7%. Many of these respondents were unaware of the newly proposed TIA definition (59%), unfamiliar with TIA mimics and predictors of post-TIA early stroke recurrence and therefore with the rationales underlying the need of emergency management of TIA. More than one third (39%) were unaware of the relevant national guidelines. Guidelines-aware respondents performed better in most part of the mailed questionnaire. CONCLUSION: Our results show that poorly updated knowledge about TIA among non-neurologists represents a potential contributing factor to the persisting sub-optimal management of the disorder. Although further studies are needed to confirm this, improved continuous medical education of this group of health care professionals appears warranted.

'Clinically definite benign multiple sclerosis', an unwarranted conceptual hodgepodge: evidence from a 30-year observational study.

BACKGROUND: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. OBJECTIVES: To assess two definitions of 'clinically definite benign multiple sclerosis' (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. METHODS: In 874 patients with definite relapsing-remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. RESULTS: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. CONCLUSIONS: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.

Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients.

BACKGROUND: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. OBJECTIVE: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. METHODS: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. RESULTS: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. CONCLUSION: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.

Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.

OBJECTIVES: The long-term impact of interferon-beta-1b (IFN) might be improved by short-term immunosuppression with mitoxantrone (MITOX) in aggressive relapsing-remitting multiple sclerosis (ARMS) patients. METHODS: In this 3-year clinical and MRI study, 109 ARMS patients (two or more relapses in the previous 12 months and one or more gadolinium (Gd)-enhancing MRI lesion) were randomised into two groups: 54 patients received MITOX monthly (12 mg/m(2); maximum 20 mg) combined with 1 g of methylprednisolone (MP) for 6 months followed by IFN for the last 27 months, and 55 patients received IFN for 3 years combined with 1 g of MP monthly for the first 6 months. The primary endpoint was the time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months. RESULTS: The time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months was delayed by 18 months in the MITOX group compared with the IFN group (p<0.012). The 3-year risk of worsening disability was reduced by 65% in the MITOX group relative to the IFN group (11.8% vs 33.6%). MITOX patients had a reduced relapse rate by 61.7%, a reduced number of Gd-enhancing lesions at month 9 and a slower accumulation of new T2 lesions at each time point. CONCLUSIONS: Although there were limitations in this investigator-academic-driven study, the data do suggest that mitoxantrone induction therapy prior to INF beta-1b may have a role in aggressive disease.

Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.

BACKGROUND: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. OBJECTIVE: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS). METHODS: Eight hundred and two patients from 12 MS centres (308 relapsing-remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6-12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after. RESULTS: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. CONCLUSION: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.

Prevalence, characteristics and comorbidities of anxiety disorders in France: results from the "Mental Health in General Population" survey (MHGP).

PURPOSE: Only a few European countries have carried out large, community-based, national surveys about psychiatric morbidity. Here is presented the first national French survey, aiming to estimate the prevalence of anxiety disorders and associated comorbidities according to sociodemographic characteristics. MATERIALS AND METHODS: The Mental Health in General Population (MHGP) database is derived from a representative national survey of the French adult population (n=36,105), conducted between 1999 and 2003. Data collection was done using an anonymous face-to-face interview. The presence of anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder) was assessed using the Mini International Neuropsychiatric Interview. RESULTS: The overall prevalence of anxiety disorders was estimated to be 21.6%, generalized anxiety disorder being the most prevalent one (12.8%). Women, young people, and people earning low income were identified as the more at risk. Major depressive episode, alcohol abuse and drug addiction frequently co-occur with anxiety disorders (28.3, 4.4 and 2.8% respectively). CONCLUSION: The MHGP study showed that anxiety disorders are highly prevalent in France with a high frequency of comorbidities. Our results highlight the need for considering anxiety disorders as a public health priority in France as well as in other European countries.

Longitudinal study of bone mineral density in children after a diagnosis of Crohn's disease.

AIM: The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution. PATIENTS AND METHODS: A total of 27 children (20 boys, seven girls), aged 12.1±2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]. RESULTS: BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ. CONCLUSION: Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay.

[Can we explain the sudden infant death syndrome? About a series of 80 cases with an autopsy in Rennes University Hospital, France in the period 1994-2007]. / Peut-on expliquer la mort inattendue du nourrisson? Réflexions à partir d'une série de 80 cas autopsiés au CHU de Rennes entre 1994 et 2007.

Sudden infant death syndrome (SIDS) is a huge hardship for parents, but also for health professionals. In 2007, 210 cases occurred in France, corresponding to a crude rate of 31.8 for 100,000 births. Between 1994 and 2007, 140 children of less than 2 years old were examined in the reference centre for SIDS in Rennes, France. We included in our study the children who were aged more than 28 days at death date, did not have a known lethal disease and were autopsied. A total of 80 children fulfilled those criteria. Post-mortem investigation included an autopsy, clinical and paraclinical exams (blood test, radiography, CT-scan...), and investigation of the circumstances of the death. Most of the cases were boys and were 2- to 5-month old. Ventral decubitus and gastrointestinal symptoms were often present. Autopsy gave elements about the causes of death in 23 cases and the other exams performed frequently showed an infectious viral context. Thanks to prevention and information campaigns about childcare done in the 1990s, SIDS incidence has largely decreased in France, but it is still too frequent. In our opinion, advice needs to be given again and again, especially concerning safe sleep practices, in order to increase adherence to these recommendations. Moreover, research should be continued to better understand this unexplained syndrome.

Influence of job seniority, hand hygiene education, and patient-to-nurse ratio on hand disinfection compliance.

Hand hygiene compliance was evaluated by direct observation in 2006 and 2007. In 2007, data on characteristics such as job seniority, hand hygiene education, and patient-to-nurse ratio during direct observations were collected. A hand hygiene promotional programme was performed between the two evaluations. Univariate and multivariate analysis identified factors associated with improved hand hygiene compliance. Between 2006 and 2007, from 761 hand hygiene opportunities, overall and partial compliance improved from 44.9% to 58% (P<0.001) and from 73.5% to 88.4% (P<0.001), respectively. In 2007, improvements in hand hygiene overall or partial compliance were seen when senior healthcare workers (HCWs) were present in the clinical area under investigation (P=0.04 or P=0.08, respectively). Partial hand hygiene compliance was significantly better in 2007 after a hand hygiene educational programme had been presented (P<0.015). Similar rates of compliance were observed whatever the patient-to-nurse ratio during the observation. Multivariate analysis identified job seniority as an independent predictor of hand hygiene compliance. Our results suggest that hand hygiene compliance is influenced by education on hand hygiene and that a senior HCW could act as a role model for other HCWs. These data should be considered when developing future hygiene interventions.